Randomized, Double-Blind Parallel-Group, Phase 3 Multicenter Study to Evaluate the Efficacy of Zelpultide Alfa in Preventing Bronchopulmonary Dysplasia (BPD) in High-Risk Preterm Neonates Compared to Standard of Care (SOC)

The goal of this Randomized, Double-Blind, Parallel-Group, Phase 3 Multicenter Study is to determine if an investigational drug, Zelpultide Alfa, can reduce the occurrence of Bronchopulmonary Dysplasia (BPD) in extremely premature babies.
The main objective is to compare the efficacy of zelpultide alfa added to standard of care (SOC) versus SOC plus placebo (air-sham) in terms of incidence of grade 2 and grade 3 bronchopulmonary dysplasia (BPD) and death in neonates at high risk for developing BPD.
Participants will be randomized 1:1 to the treatment (Zelpultide alfa plus standard of care) or placebo (air-sham plus standard of care) arms . Treatment will be administered intratracheally. Participants will receive up to 7 administrations of zelpultide alfa at 6 mg/kg or air-sham in 24 h intervals while the subjects are still intubated per standard of care.

Start Date03 Feb 2025

Sponsor / Collaborator

Airway Therapeutics, Inc.

NCT04662151

/ CompletedPhase 1

A Phase 1b, Randomized, Blinded, Dose-Determined Study Evaluating the Safety and Tolerability Profile of Intervention With AT-100 (rhSP-D) in Preterm Neonates at High Risk for the Development of Bronchopulmonary Dysplasia (BPD)

The purpose of this study is to determine if an investigational drug, AT-100, can reduce the occurrence of Bronchopulmonary Dysplasia (BPD) in babies born premature, as compared to babies born premature who receive an air-sham alone.

Start Date01 Sep 2021

Sponsor / Collaborator

Airway Therapeutics, Inc.

NCT04659122

/ TerminatedPhase 1

Phase 1b Open-label, Single Arm, Cohort Dose Escalation Study Evaluating the Safety, Tolerability, and Feasibility of Intervention With AT-100 (rhSP-D) in Intubated Patients Receiving Invasive Mechanical Ventilation With Severe COVID-19 Infection or Respiratory Failure Secondary to Severe Community Acquired Pneumonia

The purpose of this study is to determine if an investigational drug, AT-100, is safe and tolerated by adults who have severe corona virus disease 2019 (COVID-19) or respiratory failure secondary to severe community acquired pneumonia.

Start Date17 Aug 2021

Sponsor / Collaborator

Airway Therapeutics, Inc.

100 Clinical Results associated with Zelpultide alfa

100 Translational Medicine associated with Zelpultide alfa

100 Patents (Medical) associated with Zelpultide alfa

Literatures (Medical) associated with Zelpultide alfa

01 Dec 2021·Respiratory researchQ2 · MEDICINE

Surfactant protein D and bronchopulmonary dysplasia: a new way to approach an old problem

Q2 · MEDICINE

ReviewOA

Author: Kingma, Paul S ; Arroyo, Raquel

Abstract:

Surfactant protein D (SP-D) is a collectin protein synthesized by alveolar type II cells in the lungs. SP-D participates in the innate immune defense of the lungs by helping to clear infectious pathogens and modulating the immune response. SP-D has shown an anti-inflammatory role by down-regulating the release of pro-inflammatory mediators in different signaling pathways such as the TLR4, decreasing the recruitment of inflammatory cells to the lung, and modulating the oxidative metabolism in the lungs. Recombinant human SP-D (rhSP-D) has been successfully produced mimicking the structure and functions of native SP-D. Several in vitro and in vivo experiments using different animal models have shown that treatment with rhSP-D reduces the lung inflammation originated by different insults, and that rhSP-D could be a potential treatment for bronchopulmonary dysplasia (BPD), a rare disease for which there is no effective therapy up to date. BPD is a complex disease in preterm infants whose incidence increases with decreasing gestational age at birth. Lung inflammation, which is caused by different prenatal and postnatal factors like infections, lung hyperoxia and mechanical ventilation, among others, is the key player in BPD. Exacerbated inflammation causes lung tissue injury that results in a deficient gas exchange in the lungs of preterm infants and frequently leads to long-term chronic lung dysfunction during childhood and adulthood. In addition, low SP-D levels and activity in the first days of life in preterm infants have been correlated with a worse pulmonary outcome in BPD. Thus, SP-D mediated functions in the innate immune response could be critical aspects of the pathogenesis in BPD and SP-D could inhibit lung tissue injury in this preterm population. Therefore, administration of rhSP-D has been proposed as promising therapy that could prevent BPD.

01 May 2021·Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische GesellschaftQ3 · MEDICINE

Evaluation of recombinant human SP-D in the rat premature lung model

Q3 · MEDICINE

Article

Author: Raquel Arroyo ; Shawn N. Grant ; Kara R. Gouwens ; Paul S. Kingma ; Deja M. Miller

BACKGROUND:

The lungs of premature and term babies are structurally different from the adult lungs. Preterm lungs are underdeveloped, non-compliant in terms of breathing, often need mechanical ventilation and these patients commonly develop syndromes as a consequence of their prematurity, such as bronchopulmonary dysplasia (BPD). Surfactant protein SP-D could be a therapy for BPD. However, there is a need for an animal model that resembles the structural characteristics of premature lungs to test SP-D and future molecules that will target the newborn population. The aim of this study was to develop and validate a pre-clinical model of early alveolarization and structurally premature lungs in 10-day-old rats, and establish the dose safety and distribution of rhSP-D administered intratracheally to premature lungs.

METHODS:

Ten-day-old Sprague Dawley rats were selected to develop the lung model. SP-D was administered intratracheally. Bronchoalveolar lavage fluid and lungs were collected to evaluate inflammation and SP-D distribution.

RESULTS:

The 10-day-old rat pup demonstrates early alveolarization features of premature lung development and it tolerates daily intratracheal injections for up to 14 days. The intratracheal administration of rhSP-D, at a dose of 8 mg/kg, does not induce an inflammatory response or histological signs of toxicity in the premature lung, even with a daily administration for 14 days. The pharmacokinetic distribution of rhSP-D in premature lungs has a half-life of ∼9 h, and the incorporation into blood is minimal.

CONCLUSIONS:

10-day-old rats are a good pre-clinical animal model of premature lungs, and rhSP-D can be intratracheally administered at doses up to 8 mg/kg without expecting adverse reactions.

01 Aug 2020·Biochimica et biophysica acta. Proteins and proteomicsQ4 · BIOLOGY

Functional characterization of the different oligomeric forms of human surfactant protein SP-D

Q4 · BIOLOGY

Article

Author: Raquel Arroyo ; Perez-Gil, Jesus ; Moreno-Herrero, Fernando ; Kingma, Paul S ; Echaide, Mercedes ; Arroyo, Raquel

Surfactant Protein D (SP-D) is a collectin protein that participates in the innate immune defense of the lungs. SP-D mediates the clearance of invading microorganisms by opsonization, aggregation or direct killing, which are lately removed by macrophages. SP-D is found as a mixture of trimers, hexamers, dodecamers and higher order oligomers, "fuzzy balls". However, it is unknown whether there are differences between these oligomeric forms in functions, activity or potency. In the present work, we have obtained fractions enriched in trimers, hexamers and fuzzy balls of full-length recombinant human (rh) SP-D by size exclusion chromatography, in a sufficient amount to perform functional assays. We have evaluated the differences in protein lectin-dependent activity relative to aggregation and binding to E. coli, one of the ligands of SP-D in vivo. Fuzzy balls are the most active oligomeric form in terms of binding and aggregation of bacteria, achieving 2-fold binding higher than hexamers and 50% bacteria aggregation at very short times. Hexamers, recently described as a defined oligomeric form of the protein, have never been isolated or tested in terms of protein activity. rhSP-D hexamers efficiently bind and aggregate bacteria, achieving 50-60% aggregation at final time point and high protein concentrations. Nevertheless, trimers are not able to aggregate bacteria, although they bind to them. Therefore, SP-D potency, in functions that relay on the C-lectin activity of the protein, is proportional to the oligomeric state of the protein.

News (Medical) associated with Zelpultide alfa

15 Oct 2024

·pipelinereview.com

Airway Therapeutics to Launch a Multinational Phase 3 Trial of Zelpultide Alfa for Preterm Neonates at Risk of Bronchopulmonary Dysplasia

ATLANTA, GA, USA I October 15, 2024 I Airway Therapeutics , Inc. (Airway), a biopharmaceutical company developing a new class of biologics to break the cycle of injury and inflammation for patients with respiratory and inflammatory diseases, announced today it will launch a multinational Phase 3 clinical trial in December 2024 of zelpultide alfa (rhSP-D) for prevention of bronchopulmonary dysplasia (BPD) and minimization of resulting lung damage in preterm infants. As many as 2.5 million very preterm infants globally are at risk of developing BPD from lung damage caused by mechanical ventilation and oxygen support. BPD can cause lifelong complications such as asthma and pneumonia as well as growth and developmental problems. The pivotal trial will begin in Italy and Spain and expand to additional countries in 2025. The randomized, double-blind, parallel-group study will enroll 316 neonates born between 23 weeks and less than 28 weeks to assess the efficacy of zelpultide alfa (administered intratracheally) when added to standard of care in preventing or reducing the severity of BPD. “The approval of this Phase 3 trial is based on the successful completion of our randomized blinded Phase 1b study in the US and Europe, in which no dose limiting toxicities were found and indications of efficacy were observed,” said Airway Chairman, CEO and Chief Medical Officer Marc Salzberg, M.D. “Zelpultide alfa would be the first preventive therapy to protect babies from BPD, which is a debilitating lung disease.” Dr. Salzberg added, “We are grateful to the parents of these fragile patients participating in our ground-breaking clinical trials, and we look forward to further improving the health outcomes for babies born very prematurely, hopefully representing a significant advancement in an area needing new solutions.” These very early preterm born babies lack a vital protein in their lungs called SP-D, which is essential to the lung’s immune defense in reducing inflammation and infection while modulating immune responses. Airway Therapeutics has developed zelpultide alfa, the only recombinant version of human SP-D developed as a replacement therapy to protect the infants’ lungs. “We feel so honored and blessed to work on the development of zelpultide alfa for prevention of BPD. The neonatology community has big hopes in this novel scientifically well supported intervention for BPD,” stated Prof. Daniele De Luca and Prof. Maximo Vento, Principal Investigators. Zelpultide alfa has been granted orphan drug designation in US and Europe. The global market for preventing BPD is estimated in excess of $5 billion annually. About Airway Therapeutics Airway Therapeutics is a biopharmaceutical company developing a new class of biologics to break the cycle of injury and inflammation for patients with respiratory and inflammatory diseases, beginning with the most vulnerable populations. The company is advancing zelpultide alfa, a novel recombinant human protein hSP-D that reduces inflammation and infection in the body while modulating the immune response. Zelpultide alfa is Airway’s first candidate in development for prevention of BPD in very preterm infants and for treatment of COVID/CAP in seriously ill mechanically ventilated patients. SOURCE: Airway Therapeutics

Orphan DrugPhase 3Phase 2Phase 1

05 Jun 2023

·www.biospace.com

Airway Therapeutics Completes Enrollment in Phase 1b Trial of Zelpultide Alfa (AT-100) for Very Preterm Infants at Risk for Bronchopulmonary Dysplasia

Favorable safety pro also in fourth and final cohort including babies born at earliest gestational age of 23 to 24 weeks Interim analysis is complete and full results are expected by October 2023 Company expects to begin a Phase 3 trial by end of 2023 ATLANTA--(BUSINESS WIRE)-- Airway Therapeutics, Inc., a biopharmaceutical company developing a new class of biologics to break the cycle of injury and inflammation for patients with respiratory and inflammatory diseases, announced today it successfully completed enrollment in its Phase 1b trial of zelpultide alfa for preventive use in very preterm infants at risk for bronchopulmonary dysplasia (BPD). The last of 12 patients recruited into the fourth and final cohort of the study has been treated. These infants, born at 23 to <29 weeks, received daily treatment up to 7 days at the highest dose of zelpultide alfa (rhSP-D). The fourth cohort began recruitment March 28, 2023, following a Data Safety Monitoring Committee (DSMC) report finding no safety concerns at the conclusion of the trial’s dose escalation portion, and included the extremely preterm neonates born as early as weeks 23 and 24. “We are very pleased to report that the recruitment of the first clinical study with zelpultide alfa has been successfully completed according to protocol,” said Airway CEO and Chief Medical Officer Marc Salzberg, M.D. “This is another major step in the development of this novel drug for the prevention of BPD in very preterm born babies.” An interim analysis of the Phase 1b has been completed, and full trial results are expected by October 2023. The company plans to begin a Phase 3 trial by the end of 2023 which will involve at least 80 hospitals in North America and across Europe. As many as 2.5 million very preterm infants globally are at risk of developing BPD from lung damage caused by mechanical ventilation and oxygen support. Babies who develop BPD can suffer lifelong complications such as asthma and pneumonia as well as growth and developmental problems. Zelpultide alfa is a recombinant version of the endogenous human SP-D, a protein essential to the lung’s immune defense in reducing inflammation and infection while modulating immune responses. The biologic is administered intratracheally during mechanical ventilation. The Phase 1b trial is a randomized, blinded, air-sham controlled study to establish the safety and tolerability of zelpultide alfa. A total of 37 infants were enrolled at 20 hospitals in the U.S. and Spain. The 25 infants in the dose escalation portion were born at 25 weeks to <29 weeks gestational age. The FDA and European Medicines Agency have granted orphan drug status to zelpultide alfa. About Airway Therapeutics Airway Therapeutics is a biopharmaceutical company developing a new class of biologics to break the cycle of injury and inflammation for patients with respiratory and inflammatory diseases, beginning with the most vulnerable populations. The company is advancing zelpultide alfa, a novel recombinant human protein hSP-D that reduces inflammation and infection in the body while modulating the immune response. Zelpultide alfa is Airway’s first candidate in development for prevention of BPD in very preterm infants and for treatment of COVID/CAP in seriously ill mechanically ventilated patients. View source version on businesswire.com: Contacts Meghan Riley riley@airwaytherapeutics.com Source: Airway Therapeutics, Inc. View this news release online at:

Phase 1Orphan DrugPhase 2Immunotherapy

05 Jun 2023

·www.airwaytherapeutics.com

Airway Therapeutics Completes Enrollment in Phase 1b Trial of Zelpultide Alfa (AT-100) for Very Preterm Infants at Risk for Bronchopulmonary Dysplasia

Favorable safety profile confirmed also in fourth and final cohort including babies born at earliest gestational age of 23 to 24 weeks Interim analysis is complete and full results are expected by October 2023 Company expects to begin a Phase 3 trial by end of 2023 ATLANTA, GEORGIA (June 5, 2023) – Airway Therapeutics, Inc., a biopharmaceutical company developing a new class of biologics to break the cycle of injury and inflammation for patients with respiratory and inflammatory diseases, announced today it successfully completed enrollment in its Phase 1b trial of zelpultide alfa for preventive use in very preterm infants at risk for bronchopulmonary dysplasia (BPD). The last of 12 patients recruited into the fourth and final cohort of the study has been treated. These infants, born at 23 to <29 weeks received daily treatment up to 7 days at the highest dose of zelpultide alfa (rhSP-D). The fourth cohort began recruitment March 28, 2023, following a Data Safety Monitoring Committee (DSMC) report finding no safety concerns at the conclusion of the trial’s dose escalation portion, and included the extremely preterm neonates born as early as weeks 23 and 24. “We are very pleased to report that the recruitment of the first clinical study with zelpultide alfa has been successfully completed according to protocol,” said Airway CEO and Chief Medical Officer Marc Salzberg, M.D. “This is another major step in the development of this novel drug for the prevention of BPD in very preterm born babies.” An interim analysis of the Phase 1b has been completed, and full trial results are expected by October 2023. The company plans to begin a Phase 3 trial by the end of 2023 which will involve at least 80 hospitals in North America and across Europe. As many as 2.5 million very preterm infants globally are at risk of developing BPD from lung damage caused by mechanical ventilation and oxygen support. Babies who develop BPD can suffer lifelong complications such as asthma and pneumonia as well as growth and developmental problems. Zelpultide alfa is a recombinant version of the endogenous human SP-D, a protein essential to the lung’s immune defense in reducing inflammation and infection while modulating immune responses. The biologic is administered intratracheally during mechanical ventilation. The Phase 1b trial is a randomized, blinded, air-sham controlled study to establish the safety and tolerability of zelpultide alfa. A total of 37 infants were enrolled at 20 hospitals in the U.S. and Spain. The 25 infants in the dose escalation portion were born at 25 weeks to <29 weeks gestational age. The FDA and European Medicines Agency have granted orphan drug status to zelpultide alfa. About Airway Therapeutics Airway Therapeutics is a biopharmaceutical company developing a new class of biologics to break the cycle of injury and inflammation for patients with respiratory and inflammatory diseases, beginning with the most vulnerable populations. The company is advancing zelpultide alfa, a novel recombinant human protein hSP-D that reduces inflammation and infection in the body while modulating the immune response. Zelpultide alfa is Airway’s first candidate in development for prevention of BPD in very preterm infants and for treatment of COVID/CAP in seriously ill mechanically ventilated patients. Media contact: Meghan Riley riley@airwaytherapeutics.com

Phase 1Orphan DrugPhase 2Clinical ResultImmunotherapy

100 Deals associated with Zelpultide alfa

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bronchopulmonary Dysplasia	Phase 3	Italy	Airway Therapeutics, Inc.	13 Jun 2024
Community Acquired Pneumonia	Phase 1	United States	Airway Therapeutics, Inc.	17 Aug 2021
COVID-19	Phase 1	United States	Airway Therapeutics, Inc.	17 Aug 2021
Respiratory Failure	Phase 1	United States	Airway Therapeutics, Inc.	17 Aug 2021
Asthma	Preclinical	United States	Airway Therapeutics, Inc.	01 Mar 2025
Pulmonary Disease, Chronic Obstructive	Preclinical	United States	Airway Therapeutics, Inc.	01 Mar 2025
Respiratory Distress Syndrome, Acute	Preclinical	United States	Airway Therapeutics, Inc.	01 Mar 2025
Influenza, Human	Preclinical	United States	Airway Therapeutics, Inc.	14 Dec 2023
Respiratory Syncytial Virus Infections	Preclinical	United States	Airway Therapeutics, Inc.	14 Dec 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04662151 (ATS2024) Manual	Phase 1	Bronchopulmonary Dysplasia	37	zelpultide alfa	zvwinvqsat(bhqeejiaxq) = uyfjzoguwu ezxzlqxlxn (ifreodglne ) View more	Positive	22 May 2024

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